Cavaillon and Adib-Conquy Critical Care 2010, 14:167

http://ccforum.com/content/14/3/167

CO M M E N TA R Y

Immune status in sepsis: the bug, the site of

infection and the severity can make the difference
Jean-Marc Cavaillon* and Minou Adib-Conquy
See related research by Gogos et al., http://ccforum.com/content/14/3/R96

Abstract
Studying a large number of patients with sepsis,
the Hellenic sepsis study group led by Evangello
Giamarellos-Bourboulis emphasizes that the nature
of the bacterial infection, its origin (community or
nosocomial), its site, and its severity exert different
pressures on the immune system. Their study illustrates
the heterogeneity of patients with sepsis and points
out that numerous key parameters of severe infection
influence immune status.

In a study published in this issue of Critical Care, Gogos

and colleagues [1] investigated the inuence of the type
of bacterial infection, the compartment where it occurs,
its origin (community or nosocomial), and its severity
(sepsis versus severe sepsis or septic shock) on lymphopenia, on the respective number of mononuclear cell
subsets, on apoptosis of circulating mononuclear cells,
and on HLA-DR expression on monocytes. The same
group had already reported that tumor necrosis factor
(TNF) and interleukin (IL)-6 production by lipopolysaccharide (LPS)-stimulated monocytes was lower in sepsis
patients with ventilator-associated pneumonia than in
patients with sepsis due to other types of infections [2].
These analyses permit clinicians to monitor sepsis
patients immune status, which undergoes numerous
modications gathered under the term compensatory
anti-inammatory response syndrome [3].
Lymphopenia is a hallmark of sepsis. It aects most
lymphocyte subsets, although some divergent observations for B lymphocytes exist [4-6]. Importantly, lymphopenia is accompanied by modications of the CD4+/CD8+
ratio and the relative percentage of cellular subsets. For
example, among lymphocytes, the percentages of Treg
*Correspondence: jean-marc.cavaillon@pasteur.fr
Institut Pasteur, Unit Cytokines & Inflammation, Dpartement Infection et
Epidmiologie, 28 rue Dr. Roux F-75015 Paris - France

2010 BioMed Central Ltd

2010 BioMed Central Ltd

(regulatory T) [7] and of natural killer (NK) [8] cells are

enhanced. Lymphopenia already has been associated
with bacteremia [9], has been found to be more severe in
patients with Gram-positive infection than in those with
Gram-negative infection [4], and has been found to
inversely correlate with outcome [10]. It can be mimicked
by injections of live bacteria, LPS, IL-1, or TNF in animal
models. The mechanisms that lead to lymphopenia are
mainly a redistribution of activated cells that leave the
blood compartment to migrate toward the tissues,
particularly toward lymphatic tissues, and the occurrence
of apoptosis. Apoptosis of lymphocytes during human
sepsis was revealed by the Hotchkiss group [11] when
studying the spleens of patients who died of sepsis. Le
Tulzo and colleagues [12] showed that apoptosis of
circulating lymphocytes was signicantly lower in
patients with sepsis than in those with septic shock.
Hotchkiss and colleagues [13] showed that apoptosis was
aecting circulating NK cells, B lymphocytes, and CD4+
and CD8+ T lymphocytes. The reduced HLA-DR expression on CD14+ monocytes is another hallmark of sepsis
and systemic inammatory response syndrome. It is a
useful prognosis marker of intensive care patients and
correlates with the occurrence of sepsis [14]. Measurements performed a few days after the onset of sepsis
appear as a prognosis marker, and low expression correlates with poor outcome [15]. IL-10 and glucocorticoids
are the main mediators that lower HLA-DR expression,
although they act dierently on CD14HIGHCD16NEG and
CD14LOWCD16POS monocyte subsets [16].
The present study illustrates the importance of being
careful when comparing dierent reports, which often
include dierent types of patients with sepsis. The
heterogeneity of the patients gathered under the term
sepsis is a nightmare for anyone who wishes to submit
grant applications or articles, since reviewers can easily
argue that the studied group is ill dened and too heterogeneous! This study further emphasizes the diculty of
reaching denite conclusions on patients with sepsis
when considered as a global group. The conclusions
drawn for sepsis patients with pyelonephritis may not be
true for sepsis patients with community-acquired

Cavaillon and Adib-Conquy Critical Care 2010, 14:167

http://ccforum.com/content/14/3/167

pneumonia or intra-abdominal infection. However,

although the authors report dierences, these dierences
were minimal. Only community-acquired pneumonia
was associated with a higher number of NK cells as
compared with the other groups, and only intraabdominal infection was associated with an enhanced
number of CD8+ cells. The latter group was the only one
with a signicantly enhanced number of apoptotic CD8+
cells. Reduced expression of HLA-DR on CD14+ cells was
seen mainly in patients infected with Klebsiella
pneumoniae or Acinetobacter baumanii. Surprisingly,
when patients with sepsis were compared with those with
severe sepsis and septic shock, the number of signicant
dierences in terms of the number of circulating NK
cells, CD4+ T lymphocytes, CD8+ T lymphocytes, and B
lymphocytes was limited to community-acquired pneumonia and intra-abdominal infection. Such a dierence
was not seen in patients with nosocomial pneumonia,
pyelonephritis, or bacteremia. Enhanced apoptosis of NK
and NKT cells was seen mainly in severe sepsis or septic
shock caused by nosocomial pneumonia. Finally, HLADR expression was particularly reduced in patients with
severe sepsis or septic shock due to pyelonephritis or
intra-abdominal infection. Altogether, it is heartening to
note that there were fewer dierences than similarities
between the dierent sepsis subgroups. Who else but
Hippocrates can oer us a conclusion for this study from
Greece: It is more important to know what sort of person
has a disease than to know what sort of disease a person has.
Abbreviations
IL, interleukin; LPS, lipopolysaccharide; NK, natural killer; TNF, tumor necrosis
factor.

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Competing interests
The authors declare that they have no competing interests.

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Published: 18 June 2010

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doi:10.1186/cc9046
Cite this article as: Cavaillon J-M, Adib-Conquy M: Immune status in sepsis:
the bug, the site of infection and the severity can make the difference.
Critical Care 2010, 14:167.